Non-small Cell Lung Cancer (NSCLC), Colorectal Cancer (CRC), Pancreatic Ductal Adenocarcinoma (PDAC), Advanced Solid Tumors
Conditions
Keywords
KRAS G12D (ON), NSCLC, CRC, PDAC, Non-small Cell Lung Cancer, Lung Cancer, Colorectal Cancer, Colon Cancer, Pancreatic Cancer, Metastatic Cancer, Pancreatic Ductal Adenocarcinoma, Pancreatic Neoplasms, Colorectal Neoplasms, Gastrointestinal Neoplasms, KRAS, Colonic Neoplasms
Brief summary
This study is to evaluate the safety and tolerability of RMC-9805 as monotherapy and in combination with RMC-6236 in adults with KRAS G12D-mutant solid tumors.
Detailed description
This is an open-label, multicenter, Phase 1/1b study of RMC-9805, a selective and orally bioavailable KRAS G12D(ON) inhibitor, in subjects with KRASG12D-mutant solid tumors to evaluate the safety, tolerability, pharmacokinetics (PK), and preliminary clinical activity. The study consists of two arms: RMC-9805 monotherapy arm and RMC-9805 plus RMC-6236 combination arm. Both arms consist of two parts: Part 1- dose exploration and Part 2- dose expansion.
Sponsors
Revolution Medicines, Inc.
Study design
Allocation
NON_RANDOMIZED
Intervention model
PARALLEL
Primary purpose
TREATMENT
Masking
NONE
Intervention model description
The monotherapy arm of RMC-9805; the combination arm of RMC-9805 plus RMC-6236
Eligibility
Sex/Gender
ALL
Age
18 Years to No maximum
Healthy volunteers
No
Inclusion criteria
* Pathologically documented, locally advanced or metastatic solid tumor with a KRAS G12D-mutation * Received and progressed or been intolerant to prior standard therapy (including targeted therapy) appropriate for tumor type and stage * ECOG performance status 0 or 1 * Adequate organ function
Exclusion criteria
* Primary central nervous system (CNS) tumors * Known or suspected leptomeningeal or active brain metastases or spinal cord compression * Known or suspected impairment of gastrointestinal function that may prohibit ability to swallow or absorb an oral medication * Participant was previously treated with an investigational KRAS G12D inhibitor, pan- or multi-RAS inhibitor, or had prior therapy with any direct RAS-targeted therapy (eg, degraders and inhibitors) Other inclusion/
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Adverse events | Up to 3 years | Incidence and severity of treatment-emergent Adverse Events (AEs) and serious AEs and clinically significant changes in laboratory values, ECGs, and vital signs |
| Dose Limiting Toxicities | 21 days | Number of participants with Dose Limiting Toxicities (DLTs) |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| Maximum Observed Blood Concentration (Cmax) of RMC-9805 as monotherapy and in combination with RMC-6236, and Cmax of RMC-6236 in combination with RMC-9805 | up to 21 weeks | Cmax |
| Time to Reach Maximum Blood Concentration (Tmax) of RMC-9805 as monotherapy and in combination with RMC-6236, and Tmax of RMC-6236 in combination with RMC-9805 | up to 21 weeks | Tmax |
| Area Under Blood Concentration Time Curve (AUC) of RMC-9805 as monotherapy and in combination with RMC-6236, and AUC of RMC-6236 in combination with RMC-9805 | up to 21 weeks | AUC |
| Ratio of accumulation of RMC-9805 from a single dose to steady state with repeated dosing as monotherapy and in combination with RMC-6236, and ratio of accumulation of RMC-6236 in combination with RMC-9805 | up to 21 weeks | accumulation ratio |
| Time to Response (TTR) | up to 3 years | Assess per RECIST v1.1 |
| Overall Response Rate (ORR) | up to 3 years | Assess per RECIST v1.1 |
| Duration of Response (DOR) | up to 3 years | Assess per RECIST v1.1 |
| Disease Control Rate (DCR) | up to 3 years | Assess per RECIST v1.1 |
| Elimination Half-Life (t1/2) of RMC-9805 as monotherapy and in combination with RMC-6236, and t1/2 of RMC-6236 in combination with RMC-9805 | up to 21 weeks | t1/2 |
| Progression-Free Survival (PFS) | up to 3 years | Assess per RECIST v1.1 |
Countries
United States
Contacts
Primary ContactRevolution Medicines, Inc.
Outcome results
None listed